HIPEC during Surgery for Ovarian Cancer

(HIPEC Trial)

Overseen By Study Nurse

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must be taking: Platinum chemotherapy

Disqualifiers: Radiation, Adhesive disease, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 months

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it does require that you have completed a specific course of platinum-based chemotherapy before participating.

What data supports the effectiveness of the treatment HIPEC during surgery for ovarian cancer?

Research shows that combining surgery with heated chemotherapy (HIPEC) can be effective for treating cancers in the abdomen, including ovarian cancer, especially in patients who have not responded well to other treatments. This approach has been used successfully in other types of abdominal cancers, suggesting it may help improve outcomes for ovarian cancer patients as well. ^{1 2 3 4 5}

Is HIPEC during surgery for ovarian cancer generally safe for humans?

HIPEC, when combined with surgery, has been associated with significant risks, including long hospital stays and moderate risk of death around the time of surgery. However, some studies suggest that these risks can be reduced with experience and careful management. ^{1 2 5 6 7}

How is the HIPEC treatment with carboplatin during surgery for ovarian cancer different from other treatments?

HIPEC with carboplatin is unique because it involves delivering heated chemotherapy directly into the abdominal cavity during surgery, which can enhance the drug's effectiveness against cancer cells compared to traditional intravenous chemotherapy. ^{1 4 8 9 10}

What is the purpose of this trial?

The purpose of this research study is to see if it is feasible to receive heated chemotherapy or heated intraperitoneal chemotherapy (HIPEC) inserted directly into the abdomen at the time of a Second Look Reassessment Surgery and to monitor any effects good or bad that this has on participants' health.

Research Team

Laurel Berry, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for adults over 18 with specific types of ovarian, fallopian tube, or peritoneal cancer. Participants must have completed certain surgeries and chemotherapy within a set timeframe, have no current evidence of disease, and meet specific health criteria like organ function. Pregnant individuals or those with recent infections, severe allergies to carboplatin, or unstable health conditions are excluded.

Inclusion Criteria

Ability to understand and the willingness to sign an IRB-approved informed consent document

I show no signs of cancer after chemotherapy, confirmed by exams and tests.

My surgery removed all visible cancer before starting chemotherapy.

Exclusion Criteria

You have had allergic reactions to drugs similar to carboplatin.

Pregnancy

I have not had radiation therapy to my abdomen or pelvis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo second look laparoscopy and may receive hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin if visible signs of cancer are present.

Up to 3 months

Follow-up

Participants are monitored for quality of life and toxicities using the FACT-O questionnaire and CTCAE criteria.

Up to 6 months

Treatment Details

Interventions

• Carboplatin
• Second look laparoscopy reassessment surgery (SLLRS)

Trial Overview The study tests the feasibility and impact on quality of life when administering heated chemotherapy (HIPEC) during a second look laparoscopy surgery in patients who've had prior treatment for certain cancers. The FACT-O questionnaire will assess participants' quality of life outcomes.

Participant Groups

Group I: Second Look Laparoscopy and HIPEC with Carboplatin Experimental Treatment 3 Interventions

Laparoscopic assessment of disease status of the peritoneal cavity with lysis of adhesions as necessary noting either no gross residual disease or minimal residual disease prior to or after resection. This is performed prior to establishment of a peritoneal perfusion circuit and hyperthermic intraperitoneal chemotherapy.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving 122 patients undergoing 124 cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CS-HIPEC) procedures, the in-hospital mortality rate was nearly zero, and the 30-day mortality rate was only 1.6%, indicating a significant improvement in safety for this treatment approach.

Despite the low mortality rates, the study reported a high overall morbidity rate of 56.5%, with major complications occurring in 29.8% of cases, highlighting the need for further research to optimize patient outcomes in the treatment of peritoneal carcinomatosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggressive surgical management of peritoneal carcinomatosis with low mortality in a high-volume tertiary cancer center. Gusani, NJ., Cho, SW., Colovos, C., et al.[2022]

In a study of 15 patients with peritoneal carcinomatosis, the combination of cytoreductive surgery (CS) followed by intraperitoneal hyperthermic chemotherapy (IPHC) resulted in a median survival time of 8.4 months, which aligns with previous research findings.

The treatment was associated with significant surgical interventions, including bowel resections and blood transfusions, indicating a complex perioperative course, and highlights the need for further research to explore factors influencing survival and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy in the treatment of peritoneal carcinomatosis. Gammon, DC., Dutton, T., Piperdi, B., et al.[2019]

Cytoreductive surgery combined with intraperitoneal hyperthermic chemoperfusion (IHCP) shows a high risk of postoperative complications (44.3%), but with proper patient selection and care, most complications can be managed effectively.

Completeness of cancer resection and patient age are significant predictors of postoperative morbidity, highlighting the importance of thorough surgical techniques and careful patient assessment in improving outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of peritoneal carcinomatosis by cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion (IHCP): postoperative outcome and risk factors for morbidity. Roviello, F., Marrelli, D., Neri, A., et al.[2022]

In a study of 32 patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreductive surgery (CRS) for endometrial and epithelial ovarian cancer, the procedure showed a low operative mortality rate of 3% and a severe morbidity rate of 12%, indicating it is relatively safe.

Among the 30 patients with epithelial ovarian cancer, the 1-year overall survival rate was 69.7%, and for the platinum-resistant subgroup, the median overall survival was 14 months, suggesting that HIPEC can provide promising short-term outcomes even in challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Clinical Analysis of Hyperthermic Intraperitoneal Chemotherapy in Gynecological Cancers: Technical Details, Tolerability, and Efficacy. Minareci, Y., Tosun, OA., Sozen, H., et al.[2022]

In a study of 33 patients undergoing cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion (IPHC), complete removal of cancer was achieved in 63% of cases, indicating the treatment's potential efficacy for peritoneal malignancies.

The procedure was associated with a 27% rate of major complications but no perioperative deaths, suggesting that with careful surgical techniques, the risks can be managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced morbidity following cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion. Ahmad, SA., Kim, J., Sussman, JJ., et al.[2007]

The maximum tolerated dose (MTD) of carboplatin for intraperitoneal hyperthermic chemotherapy (IPHC) was established at 1000 mg/m², as higher doses led to significant toxicity.

Patients who received IPHC at the MTD were able to complete standard systemic chemotherapy afterward, and repeat IPHC was safely performed during second look surgeries without severe toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal hyperthermic chemotherapy using carboplatin: a phase I analysis in ovarian carcinoma. Lentz, SS., Miller, BE., Kucera, GL., et al.[2013]

In a study of 205 patients undergoing cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP) for peritoneal surface malignancies, the major morbidity rate was 12%, with an operative mortality rate of only 0.9%, indicating that the procedure is relatively safe.

The study identified that the extent of cytoreduction and a higher dose of cisplatin (≥240 mg) during IPHP were significant risk factors for major complications, suggesting that careful management of these factors is crucial for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion: analysis of morbidity and mortality in 209 peritoneal surface malignancies treated with closed abdomen technique. Kusamura, S., Younan, R., Baratti, D., et al.[2022]

In a phase II study involving 98 patients with recurrent ovarian cancer, hyperthermic intraperitoneal chemotherapy (HIPEC) using carboplatin was found to be well tolerated, with no perioperative mortality and similar postoperative toxicity compared to standard treatment.

However, HIPEC did not demonstrate superior clinical outcomes, as the median progression-free survival was shorter in the HIPEC group (12.3 months) compared to the standard treatment group (15.7 months), leading to the conclusion that HIPEC with carboplatin is not recommended during secondary cytoreductive surgery for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study. Zivanovic, O., Chi, DS., Zhou, Q., et al.[2023]

In a multicenter phase-I study involving 30 patients with initially unresectable ovarian cancer, the recommended dose of cisplatin for hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant chemotherapy was determined to be 70 mg/m², as higher doses led to significant dose-limiting toxicities (DLTs).

The study found that at the highest dose of 80 mg/m², there were serious adverse events including renal failure and hemorrhage, highlighting the importance of careful dose selection to minimize toxicity while maximizing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer. Gouy, S., Ferron, G., Glehen, O., et al.[2022]

In a study of 25 patients with advanced-stage ovarian cancer, cytoreductive surgery combined with carboplatin HIPEC showed no deaths or severe adverse events (grade 4-5), indicating a favorable safety profile.

While 44% of patients experienced at least one grade 3 adverse event, primarily infections and neutropenia, the overall morbidity was considered acceptable, supporting the feasibility of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with carboplatin used for ovarian, tubal, and primary peritoneal cancer. Mikkelsen, MS., Christiansen, T., Petersen, LK., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Aggressive surgical management of peritoneal carcinomatosis with low mortality in a high-volume tertiary cancer center. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy in the treatment of peritoneal carcinomatosis. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Treatment of peritoneal carcinomatosis by cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion (IHCP): postoperative outcome and risk factors for morbidity. [2022]

4. Turkey pubmed.ncbi.nlm.nih.gov

A Retrospective Clinical Analysis of Hyperthermic Intraperitoneal Chemotherapy in Gynecological Cancers: Technical Details, Tolerability, and Efficacy. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Reduced morbidity following cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion. [2007]

6. United States pubmed.ncbi.nlm.nih.gov

Intraperitoneal hyperthermic chemotherapy using carboplatin: a phase I analysis in ovarian carcinoma. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion: analysis of morbidity and mortality in 209 peritoneal surface malignancies treated with closed abdomen technique. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with carboplatin used for ovarian, tubal, and primary peritoneal cancer. [2019]